10758
Build Your Own ‘Medicare for All’ Plan. Beware: There Are Tough Choices. - The New York Times
Most plans would also keep premiums, though some would have subsidies for low-income families. But a few, including from Representative Pramila Jayapal and the Congressional Progressive Caucus, would do away with premiums entirely.
HealthCare  Economics  Politics 
yesterday
Value-Based Insurance Design
"Value-based insurance design" aims to increase health care quality and decrease costs by using financial incentives to promote cost efficient health care services and consumer choices. Health benefit plans can be designed to reduce barriers to maintaining and improving health. By covering preventive care, wellness visits and treatments such as medications to control blood pressure or diabetes at low to no cost, health plans may save money by reducing future expensive medical procedures. Benefit plans may create disincentives as well, such as high cost-sharing, for health choices that may be unnecessary or repetitive, or when the same outcome can be achieved at a lower cost. To decide what procedures are the most effective and cost efficient, insurance companies may use evidence-based data to design their plans. Good data about the effectiveness of value-based insurance design are limited, but early results have been promising. 

This webpage is designed to provide information about value-based insurance design, its role in the Affordable Care Act, examples of its use, and information about complementary and related cost containment strategies.    
HealthCare  Economics 
yesterday
Pembrolizumab Plus Axitinib a New Standard in Metastatic RCC
NEW YORK (Reuters Health) - First-line treatment with the anti-PD-1 immunotherapy pembrolizumab plus the VEGF-targeted tyrosine-kinase inhibitor axitinib extended overall survival and progression-free survival in patients with clear-cell metastatic renal cell carcinoma (mRCC), compared with the current standard of care, sunitinib, in the phase 3 KEYNOTE-426 trial.
"These results are exciting," co-lead investigator Dr. Thomas Powles of Barts Cancer Institute in London, England, said in a news release. "By adding pembrolizumab to a VEGF-targeted therapy, we are seeing powerful anticancer responses, including improved survival - and importantly, the results are seen across broad subgroups of patients."
Based on the results, "pembrolizumab and axitinib should be a standard of care in this setting, in my opinion," Dr. Powles said during a press briefing February 11 ahead of presentation February 16 at the 2019 Genitourinary Cancers Symposium, co-sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology and the Society of Urologic Oncology.
In the KEYNOTE-426 trial, 861 patients (mean age, 62; 73% men) with untreated clear-cell mRCC were randomly allocated to oral sunitinib once daily or to the combination of pembrolizumab given intravenously every three weeks plus oral axitinib twice daily. Treatment continued until the disease progressed, patients developed high toxicity, or they dropped out of the study.

At a median follow-up of 12.8 months, combination therapy was associated with a 47% reduction in the risk of death compared with sunitinib (hazard ratio, 0.53; P<0.0001).
Overall survival at 12 months was 89.9% in the combination group versus 78.3% in the sunitinib group, and at 18 months, it was 82.3% versus 72.1%. The benefits were seen irrespective of risk group or PD -L1 status, Dr. Powles noted.
Progression-free survival time was also longer with the pembrolizumab/axitinib combination than with sunitinib (15.1 months vs. 11.1 months).
More patients responded to the combination than to sunitinib (59.3% vs. 35.7%; P<0.0001) and the duration of response also favored combination therapy (median not yet reached vs. 15.2 months with sunitinib).

More than half of patients in the combination arm (59.0%) are still being treated versus 43.1% with sunitinib.
"Overall, we have not previously seen a renal cancer study which has improved response, progression-free survival, and overall survival. This is therefore a major step forward in renal cancer," Dr. Powles said in a statement.
Treatment-related side effects of grade 3 to 5 occurred in 62.9% of patients on the combination therapy compared to 58.1% on sunitinib, and there were more treatment-related discontinuations in the combination arm (25.9% vs. 10.1%).
"This is a very significant trial and it's going to have an impact on patient management going forward, as it works through the regulatory process," commented ASCO expert and briefing moderator Dr. Robert Dreicer.
immunotherapy  RCC  TKInhibitors 
yesterday
GitHub - Microsoft/Recommenders: Recommender Systems
This repository provides examples and best practices for building recommendation systems, provided as Jupyter notebooks. The examples detail our learnings on five key tasks:

Prepare Data: Preparing and loading data for each recommender algorithm
Model: Building models using various classical and deep learning recommender algorithms such as Alternating Least Squares (ALS) or eXtreme Deep Factorization Machines (xDeepFM).
Evaluate: Evaluating algorithms with offline metrics
Model Select and Optimize: Tuning and optimizing hyperparameters for recommender models
Operationalize: Operationalizing models in a production environment on Azure
Several utilities are provided in reco_utils to support common tasks such as loading datasets in the format expected by different algorithms, evaluating model outputs, and splitting training/test data. Implementations of several state-of-the-art algorithms are provided for self-study and customization in your own applications.
datascience  jupyter 
2 days ago
DBeaver Community | Free Universal Database Tool
Free multi-platform database tool for developers, SQL programmers, database administrators and analysts. Supports all popular databases: MySQL, PostgreSQL, MariaDB, SQLite, Oracle, DB2, SQL Server, Sybase, MS Access, Teradata, Firebird, Derby, etc.
Database  editors  tools 
2 days ago
Gaudy Night by Dorothy L Sayers – a weighty novel that still thrills | Dorothy L Sayers | The Guardian
The book feels so fundamental to me, now, that I find it hard to cast my mind back to a time when I hadn’t read it, and harder still to explain what it’s about, because it seems to be about everything. It’s a novel about work and the moral value of work; the importance – indeed the necessity – of finding the job you’re fitted for and doing it to the very best of your abilities. It’s about truth, and the need, in a slippery, shifting world, to find the one true thing you’re willing to defend, no matter what the personal cost. It’s about friendship, and how it ebbs and flows as you yourself grow – or stop growing. It’s about writing: what it means to write well and how to do it. It’s about love and integrity, and the thought and work and consideration that must go into establishing and maintaining a relationship of equality and mutual respect. It’s about class and sex and society between the wars. And above all, it’s about the age-old question (which at the time of writing was a fresh, new one) of whether it’s possible for a woman to have it all: to have a life of the mind and of the heart, and to do equal honour to them both.
Books 
3 days ago
'Exciting Times' With Immunotherapy for Kidney Cancer
San Francisco — Two new combination regimens are set to become new standards of care for the treatment of metastatic renal cell carcinoma (mRCC).
The new combinations contain an immunotherapy and a targeted agent.
New results with these combinations were presented here at the Genitourinary Cancers Symposium (GUCS) 2019 and were simultaneously published in the New England Journal of Medicine.
One combination is the immunotherapy pembrolizumab (Keytruda, Merck) and the vascular endothelial growth factor (VEGF)–targeted tyrosine-kinase inhibitor (TKI) axitinib (Inlyta, Pfizer). In the KEYNOTE-426 trial, the combination therapy yielded superior outcomes to the current standard of care, sunitinib (Sutent, Pfizer). As reported by Medscape Medical News, these results showed a significantly extended overall and progression-free survival for patients with previously untreated mRCC.

The other combination is the immunotherapy avelumab (Bavencio, Merck KGaA and Pfizer) and axitinib. Previously reported results from the JAVELIN Renal 101 trial showed that the combination significantly extended progression-free survival in the first-line setting in patients with advanced RCC, as compared to sunitinib. Updated results now show superior overall survival, with a 12-month rate of 89.9% vs 78.3% with sunitinib.
immunotherapy  RCC  nivolumab  TKInhibitors 
3 days ago
Gastric Acid Suppression & Oral Cancer Therapy Should Not Mix
As many as 50% of patients receiving cancer therapy take gastric acid suppressants (GAS), such as proton pump inhibitors, for medical problems such as gastric ulcers and acid reflux, but a new analysis suggests that these drugs may interact with orally administered cancer drugs and compromise their efficacy.
The report showed that clinical outcomes with the oral cancer agent pazopanib (Votrient, Novartis) in the treatment of advanced soft tissue sarcoma were significantly worse for patients who were concomitantly taking GAS.
The finding comes from a retrospective analysis of data from the phase 2 EORTC 62043 study and the phase 3 EORTC 62072 (PALETTE) study. Pazopanib was approved by the US Food and Drug Administration (FDA) in 2012 for use in the treatment of soft tissue sarcoma on the basis of the combined results of the EORTC 62072 (PALETTE).
The new analysis shows that participants in the two ​studies who were taking GAS as well as pazopanib had a 81% increased risk for death and a 49% increased risk for disease progression compared with patients who were taking pazopanib alone.
cancer 
3 days ago
Ruby on Rails Content-Security-Policy (CSP) | Rails security by bauland42
Updated 2018: The full Content Security Policy guide for Rails 5.2 (and earlier) apps.

How to add a Content Security Policy (CSP) to Rails?
The CSP HTTP header is a set of rules for the browser. You can use it to whitelist sources for scripts, styles, embedded content, and more. I.e. all other sources are disallowed.

CSP is a great way to reduce or completely remove Cross-Site-Scripting (XSS) vulnerabilities. That would wipe out the number 1 web app security problem. Why? Because an effective CSP disallows inline scripts. It only allows scripts in separate files from trusted sources.

Here's how the header looks like if you want to allow scripts only in files from the same origin and from G* Analytics:
ContentSecurityPolicy  Security  RubyOnRails 
4 days ago
Cannabis Decreases Tumor Response Rate to Nivolumab | PracticeUpdate
In this retrospective study, data from patients treated with nivolumab and cannabis were evaluated to determine the effects of cannabis on immunotherapy response and survival. Cannabis significantly reduced the response rate to immunotherapy, but was not a significant factor in terms of progression-free or overall survival. The percentage of tetrahydrocannabinol or cannabidiol did not affect response rates.
These data suggest that caution should be taken when starting immunotherapy in cannabis users.
nivolumab  immunotherapy  cannabis 
7 days ago
The truth about cheese: The terrible costs of our favourite food | New Scientist
Calculations that cheese isn't better for the climate than meat and the animal welfare implications are similar.
climate  Food  Economics 
7 days ago
Her
History
I told myself a few months ago that it would be great to build a gem to replace Rails’ ActiveResource since it was barely maintained (and now removed from Rails 4.0), lacking features and hard to extend/customize. I had built a few of these REST-powered ORMs for client projects before but I decided I wanted to write one for myself that I could release as an open-source project.

Most of Her’s core concepts were written on a Saturday morning of April 2012 (first commit at 7am!).
RubyOnRails  WebServices  RESTful 
7 days ago
How to Cut U.S. Emissions Faster? Do What These Countries Are Doing. - The New York Times
ogether, these seven policies would slash greenhouse gas emissions in the United States roughly 29 percent below 2005 levels by 2025, and roughly 50 percent by 2050, according to Energy Innovation’s climate policy modeling.

To put that in context, under the Paris climate agreement, the United States vowed to cut emissions at least 26 percent by 2025 and laid out a broad goal of reducing emissions 80 percent by midcentury. Assuming these policies worked as intended, they would take the country a big chunk of the way toward deep decarbonization.

These are not the only steps the United States could take to address global warming. Many of these policies would be politically tough to enact. But modeling their impact gives a sense of how far the country could, in theory, push down emissions by adopting some of the more forceful practices from around the world.

To cut emissions even more quickly and deeply, something the United Nations scientific panel has said is necessary to keep total global warming below 2 degrees Celsius, the United States, along with countries like China and India, would have to go well beyond anything that has been tried to date. That could include a much higher carbon price, investing in advanced clean-energy technologies, retrofitting older buildings, tackling sectors like air travel and shipping, deploying carbon capture systems to further reduce steel and cement emissions, as well as strategies to revitalize forests and curb methane and nitrogen pollution from livestock and farming.

Energy Innovation has created an interactive policy simulator, based on their energy model, that lets you see the potential impacts of a wider array of climate policies and technological advances. One takeaway: There are no silver bullets. Pushing emissions to nearly zero would require a slew of actions to clean up nearly every corner of the American economy.
Economics  Politics  climate  DataModeling 
8 days ago
Concerns Raised About Patient-Reported Outcomes in CheckMate 214 Trial | Cancer Network
PROs were assessed as an exploratory endpoint and gathered using three instruments: the Functional Assessment of Cancer Therapy–Kidney Symptom Index-19 (FKSI-19), Functional Assessment of Cancer Therapy-General (FACT-G), and EuroQol five-dimensional, three-level (EQ-5D-3L) tools.

At a median follow-up of 25.2 months, for two of the three assessment tools, patients in the combination arm reported better PROs than patients in the sunitinib arm from the start of treatment through 103 weeks, or about 2 years. For the FKSI-19 tool, which is validated for kidney cancer, the average change in the overall score between baseline and 103 weeks was 4.00 (95% CI, 1.91 to 6.09) for the combination arm compared with −3.14 (95% CI, –6.03 to –0.25) for the sunitinib arm (P < .0001). For the FACT-G tool, which is validated for cancer in general, the average change in overall score was 4.77 (95% CI, 1.73 to 7.82) for the combination arm vs −4.32 (95% CI, −8.54 to −0.11) for the sunitinib arm (P = .0005). For the EQ-5D-3L tool, however, PROs were not significantly different between treatment groups; EQ-5D-3L is validated for measuring general health status.

In addition to the potential bias of the open-label design, Mayer pointed out another concern. Despite showing better PROs, the combination arm had a higher discontinuation rate due to treatment-related adverse events vs the sunitinib arm (22% vs 12%).

“It’s hard to reconcile,” Mayer said. “[That] makes it difficult for me to go running to Ipi Nivo [ipilimumab plus nivolumab] as a drug regimen that’s going to give my patients better quality of life on the therapy,” he said.

A possible explanation for the higher discontinuation rate could be the inability to dose reduce the ipilimumab plus nivolumab combination. “If a patient can’t tolerance sunitinib, you might have some adjustments you can make to their therapy and they may still be able to stay on protocol, whereas in this particular trial, that might not have been true for Ipi Nivo,” Mayer explained.

Despite these study limitations, Mayer said that because the field is moving so quickly, he is not focused specifically on whether this one particular combination regimen is superior to sunitinib in terms of PROs. “We’ll probably find out in 6 months from now that it’s one big regimen—it’s all three of these [drugs]—so I try not to get too lost in those weeds,” he said.
RCC  nivolumab  immunotherapy  sunitinib 
8 days ago
AbbVie Biotherapeutics director leads team against cancer - San Francisco Business Times
Diane Hollenbaugh

Senior director, discovery

Company: AbbVie Biotherapeutics

HQ: Redwood City

Years at company: 5

Raised by a physician and a chemist in Chicago and the Pacific Northwest, Hollenbaugh always followed the science that she found the most interesting. As an undergrad at University of Washington, it was chemistry. And after receiving her Ph.D. in chemistry from the California Institute of Technology and completing her post-doc training at the Bristol-Myers Squibb Pharmaceutical Research Institute in Seattle, it became immunology, the study of immune systems. That spawned an interest in immuno-oncology, an area of research that aims to activate the body’s own immune system to fight cancer.

Hollenbaugh has been deep in immunology since 1991 and in immuno-oncology for the past 15 years at companies like Medarex, FivePrime Therapeutics and Schering-Plough/Merck. In 2013, she joined AbbVie Biotherapeutics in Redwood City, where she leads a team of scientists focused on developing new medicines.
immunotherapy  Caltech  Business 
8 days ago
HISTORICALTEAANDDANCE.ORG
Historical Dance & Ball Classes
2nd & 4th TUESDAY NIGHTS 7:30–9:30pm
Join us twice a month for
a fun and upbeat historical dance class.
No experience necessary.
BEGINNERS WELCOME! NO PARTNER NEEDED!

Each class features a different assortment of dances
and review of finer details of dance to improve your skills.
WE REVIEW DANCES FOR UPCOMING BALLS!
2nd & 4th Tuesday Historical Dance Classes
are held at the
SCOTTISH RITE CATHEDRAL HALL.
150 North Madison Avenue, Pasadena, CA 91101

Dance classes are $10 to attend.
SoCal 
9 days ago
More than 26 million people have taken an at-home ancestry test - MIT Technology Review
During the summer, the big four big ancestry companies all promised they wouldn’t let police into their databases without a warrant. But it was only weeks before the smallest player, Family Tree DNA, changed its mind and began allowing the FBI to upload DNA from corpses or blood spatters and surf the database just like any other customer, checking out names and who is related to who.

The unilateral change in policy—which users weren’t alerted to—is troubling because it means that our DNA, just like our posts on social media or our location data, is at the mercy of user agreements none of us have any control over or even bother to read. And that may be the biggest lesson of taking a DNA test.

“First rule of data: once you hand it over, you lose control of it. You have no idea how the terms of service will change for your ‘recreational’ DNA sample,” tweeted Elizabeth Joh, a law professor at the University of California, Davis.
9 days ago
AI can diagnose childhood illnesses better than some doctors | New Scientist
Diagnosing an illness requires taking in a lot of information and connecting the dots. Artificial intelligence may be well-suited to such a task and in recent tests one system could diagnose children’s illnesses better than some doctors.

Kang Zhang at the University of California in San Diego and his colleagues trained an AI on medical records from 1.3 million patient visits at a major medical centre in Guangzhou, China. The patients were all under 18 years old and visited their doctor between January 2016 and January 2017.

Their medical charts include text written by doctors and laboratory test results. To help the AI, Zhang and his team had human doctors annotate medical records to identify portions of text associated with the child’s complaint, their history of illness, and laboratory tests.

When tested on previously unseen cases, the AI could diagnoseglandular fever (also known as mononucleosis), roseola, influenza, chicken pox and hand-foot-mouth disease with between 90 and 97 per cent accuracy. It’s not perfect, but neither are human doctors, says Zhang.

“When you’re busy you can see 80 patients a day. And you can only grasp so much information. That’s where we potentially as human physicians might make mistakes. AI doesn’t have to sleep, it has a large memory and doesn’t lose energy,” he says.

The team compared the model’s accuracy to that of 20 paediatricians with varying years of experience. It outperformed the junior paediatricians, though the senior ones did better than the AI.

The AI could be used to triage patients in emergency departments. “Given sufficient data, AI should be able to tell if this is an urgent situation and needs referral or if it’s a cold,” says Zhang.

Chris Russell at the Alan Turing Institute in London says this won’t let people bypass doctors entirely when seeking medical treatment, because these medical records still need to be created by trained professionals, and their knowledge is key to the diagnosis. “Someone needs to be there discussing your symptoms and putting them into the machine. I don’t see how this technology could be used to take doctors out of the loop. It could be used to help them, but it’s a very long way from replacing medical professionals,” he says.

It’s possible that junior doctors who may rely on AI like this to make diagnoses could miss out on learning how to see patterns in patient complaints. And people may feel uncomfortable with this type of medical care. “If it’s deployed as an interface directly with the person where they type in their symptoms, I can see how people would be very uncomfortable with this. When you go see a doctor, you want to feel like there’s someone there who cares about you,” Russell says.

“But you don’t want to go to the emergency room and wait 5 hours because you have some pain in the abdomen that’s not appendicitis but just related to gastroenteritis or the food you ate. All those diseases have tell-tale signs, and just as we physicians ask a series of questions to drive a diagnosis, AI can do the same,” says Zhang.

He and his team are now training the AI to diagnose adult diseases, as well.

Journal reference: Nature Medicine, DOI: 10.1038/s41591-018/-0335-9
machinelearning  HealthCare  Science 
10 days ago
New Standard of Care for Metastatic Renal Cell Carcinoma
First-line therapy with a combination of an immune checkpoint inhibitor and a tyrosine kinase inhibitor (TKI) improved outcomes in patients with clear-cell metastatic renal cell carcinoma (mRCC), as compared with the current standard of care, according to new findings.
Pembrolizumab (Keytruda, Merck) and the VEGF-targeted TKI axitinib (Inlyta, Pfizer) significantly extended both overall and progression-free survival, and elicited a higher objective response rate than sunitinib (Sutent, Pfizer) in patients with previously untreated mRCC.
"The risk of death was reduced by almost 50% with pembrolizumab plus axitinib," said study author Thomas Powles, MD, professor of urology oncology at Barts Cancer Institute in London, England. "The benefit of pembrolizumab plus axitinib was seen irrespective of risk group or PD-L1 status."
Based on these results, "pembrolizumab and axitinib should be a standard of care in this setting, in my opinion." Powles added.

The KEYNOTE-426 clinical trial was conducted in 861 patients, who were randomized to receive either pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles plus axitinib 5 mg orally twice daily, or sunitinib 50 mg orally once daily for the first 4 weeks of each 6-week cycle.
Treatment was given until disease progression, intolerable toxicity, or patient/investigator decision to discontinue therapy.
Superior at All Endpoints

At a median follow-up of 12.8 months, overall survival was higher among patients receiving pembrolizumab and axitinib and was associated with a 47% reduction in the risk of death compared with sunitinib (hazard ratio [HR] 0.53; P < .0001).

The 12-month overall survival rate was 89.9% in the combination group vs 78.3% in the sunitinib group, and at 18 months, it was 82.3% vs 72.1%. These benefits were seen across all risk groups and PD-L1 status.
Median progression-free survival was 15.1 vs 11.1 months favoring combination therapy (HR 0.69; P = .0001), with a 12 month rate of 59.6% vs 42.6%. At 18 months it was 41.1% vs 32.9%.
For secondary endpoints, the overall response rate was 59.3% vs 35.7%, favoring combination therapy (P < .0001), and duration of response was also prolonged with pembrolizumab plus axitinib (median not reached vs 15.2 months).
Powles noted that 59% of the patients in the combination group are still being treated, as compared to 43.1% with sunitinib.
Grade 3-5 adverse events were slightly higher in the combination group (62.9% vs 58.1%), and more treatment discontinuations were observed in that group as well (25.9% vs 10.1%).
The study was funded by Merck Sharp & Dohme. Powles reports consulting or advisory role with Genentech/Roche, Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; other relationship with Ipsen and Bristol-Myers Squibb; honoraria from Roche/Genentech, Bristol-Myers Squibb, and Merck; research funding from AstraZeneca/MedImmune and Roche/Genentech. Other coauthors also report relationships with industry as noted in the abstract.
Genitourinary Cancers Symposium (GUCS) 2019: Abstract 543. To be presented February 16, 2019.
immunotherapy  TKInhibitors  RCC 
10 days ago
Cost-Effectiveness of Nivolumab and Ipilimumab vs Sunitinib in First-Line Intermediate- to Poor-Risk Advanced RCC | PracticeUpdate
BACKGROUND

The treatment paradigm of advanced renal cell carcinoma (RCC) has changed rapidly in recent years. In first-line treatment of intermediate- to poor-risk patients, the CheckMate 214 study demonstrated a significant survival advantage for nivolumab and ipilimumab versus sunitinib. The high cost of combined immune-modulating agents warrants an understanding of the combination's value by considering both efficacy and cost. The objective of this study was to estimate the cost-effectiveness of nivolumab and ipilimumab compared with sunitinib for first-line treatment of intermediate- to poor-risk advanced RCC from the U.S. payer perspective.

MATERIALS AND METHODS

A Markov model was developed to compare the costs and effectiveness of nivolumab and ipilimumab with those of sunitinib in the first-line treatment of intermediate- to poor-risk advanced RCC. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were based on Medicare reimbursement rates in 2017. We extrapolated survival beyond the trial closure using Weibull distribution. Model robustness was addressed in univariable and probabilistic sensitivity analyses.

RESULTS

The total mean cost per-patient of nivolumab and ipilimumab versus sunitinib was $292,308 and $169,287, respectfully. Nivolumab and ipilimumab generated a gain of 0.978 QALYs over sunitinib. The incremental cost-effectiveness ratio (ICER) for nivolumab and ipilimumab was $125,739/QALY versus sunitinib.

CONCLUSION

Our analysis established that the base case ICER in the model for nivolumab and ipilimumab versus sunitinib is below what some would consider the upper limit of the theoretical willingness-to-pay threshold in the U.S. ($150,000/QALY) and is thus estimated to be cost-effective.

IMPLICATIONS FOR PRACTICE

This article assessed the cost-effectiveness of nivolumab and ipilimumab versus sunitinib for treatment of patients with intermediate- to poor-risk metastatic kidney cancer, from the U.S. payer perspective. It would cost $125,739 to gain 1 quality-adjusted life-year with nivolumab and ipilimumab versus sunitinib in these patients.
RCC  nivolumab  sunitinib  Economics  HealthCare 
10 days ago
Universal income study finds money for nothing won't make us work less | New Scientist
Universal basic income comes in different flavours, but the essence of the idea is to give everyone a guaranteed income that covers their basic needs, like housing and food. Crucially, the income is the same for everyone all the time – it does not get reduced if, for example, a person gets a job or a salary increase.

The Finnish results were hotly anticipated because the experiment’s careful design promised robust evidence on UBI. “This is an exceptional experiment, both socially and globally,” said Pirkko Mattila, Finland’s Minister of Social Affairs and Health, at a press conference.

The experiment began in December 2016. Kela, the Social Insurance Institution of Finland, randomly selected 2000 people aged between 25 and 58 from across the country who were on unemployment benefits.

It then replaced those people’s benefits with a guaranteed payment of €560 a month. They would continue receiving the payments whether they got a job or not.

The experiment ended on 31 December 2018 and preliminary results were published this morning. It compared the income, employment status and general wellbeing of those who received the UBI with a control group of 5000 who carried on receiving benefits.

There was no difference between the two groups in terms of the number of days in employment in 2017 – both groups worked on average 49 days. The UBI trial group only earned €21 less on average than the control group during 2017.

The surveys also showed that the UBI group perceived their health and stress levels to be significantly better than in the control group.
Economics  inequality 
11 days ago
The Tinder algorithm, explained - Vox
In a (pre-Tinder) 2012 study, a team of researchers led by Northwestern University’s Eli J. Finkel examined whether dating apps were living up to their core promises. First, they found that dating apps do fulfill their promise to give you access to more people than you would meet in your everyday life. Second, they found that dating apps in some way make it easier to communicate with those people. And third, they found that none of the dating apps could actually do a better job matching people than the randomness of the universe could. The paper is decidedly pro-dating app, and the authors write that online dating “has enormous potential to ameliorate what is for many people a time-consuming and often frustrating activity.” But algorithms? That’s not the useful part.

This study, if I may say, is very beautiful. In arguing that no algorithm could ever predict the success of a relationship, the authors point out that the entire body of research on intimate relationships “suggests that there are inherent limits to how well the success of a relationship between two individuals can be predicted in advance of their awareness of each other.” That’s because, they write, the strongest predictors of whether a relationship will last come from “the way they respond to unpredictable and uncontrollable events that have not yet happened.” The chaos of life! It bends us all in strange ways! Hopefully toward each other — to kiss! (Forever!)

The authors conclude: “The best-established predictors of how a romantic relationship will develop can be known only after the relationship begins.”
DataMining 
11 days ago
Immune Response Markers in Matched RCC Tissue Specimens
Results: A large minority of patients had discordant expression of PD-1 (31.2%), PD-L1 (22.5%), or PD-L2 (21.5%) between primary and metastatic sites. The expression of the novel marker PD-L2 correlated with both PD-1 (r = 0.47, P = .02) and PD-L1 (r = 0.67, P < .001) in metastatic deposits.
Conclusions: This study demonstrates that renal clear cell carcinoma primary tumors and metastatic deposits have some discordance in the expression of PD-L1, PD-1, and PD-L2.
Introduction
Metastatic renal cell carcinoma (RCC) has been a difficult disease to treat historically with minimal response to cytotoxic chemotherapy and high mortality rates. Immunotherapy had been used in RCC with only limited success such as with high-dose interleukin 2 (IL-2), which induces approximately 5% to 10% of patients into a durable remission.[1] Treatment outcomes have improved with the introduction of vascular endothelial growth factor (VEGF)–targeted therapies in the past decade, although durable responses are still uncommon. The understanding of the interplay between the tumor and the immune system has led to the development of immune checkpoint inhibitors that are active in many solid tumors, including RCC. Nivolumab, an anti–PD-1 antibody, was recently approved as a treatment for VEGF-refractory metastatic RCC. A phase III trial compared nivolumab with everolimus and showed a significant overall survival benefit.[2] Similarly, pembrolizumab, another PD-1 inhibitor, and atezolizumab, a PD-L1 antibody, are being investigated in combination with VEGF inhibitors with encouraging initial activity and ongoing phase 3 trials.[3] As immune checkpoint inhibitors and other targeted therapies continue development in RCC, there will be an increasing need to identify patients who are more likely to benefit to inform clinical decisions.

The expression of the PD-L1 ligand on the tumor cell surface is a logical choice as a marker of response to PD-1 inhibitors. In the abovementioned phase III trial of nivolumab, the hazard ratio for overall survival benefit of nivolumab over everolimus was nearly identical regardless of PD-L1 expression.[2] The anti–PD-L1 antibody atezolizumab also failed to show an association between response and PD-L1 expression in early phase studies.[4] Several hypotheses have been forwarded to explain this lack of association. One hypothesis is that there are considerable differences in expression of PD-L1 in metastatic lesions compared with primary tumors since metastatic deposits adapt under immune selection pressures. Some studies have demonstrated this to be the case in RCC. Discordant tumor cell PD-L1 staining between primary tumors and matched metastases was observed in 20% of clear cell kidney tumors in one analysis.[5] Similarly, PD-L1 expression has been found to be weakly correlated between metastasis and primary kidney tumors in another series.[6] Another hypothesis involves the presence of other clinically significant ligands apart from PD-L1. An example of such an alternative ligand is PD-L2.[7] The role of PD-L2 and its differential expression in metastatic sites and kidney cancer primaries has not been examined previously.
Macrophage and T-cell infiltration of tumors may also be important determinants of treatment response. Macrophage polarization into tolerance-promoting (M2) and antitumor phenotypes (M1) has been described.[8] M1 and M2 macrophages are identifiable by HLA-DR and CD163 staining, respectively.[9,10] T-cell subtypes involved in the tumor–immune system interaction include the regulatory and cytotoxic T cells. Regulatory T cells express FOXP3 and are active in increasing immune tolerance, resulting in muting of the immune-mediated anticancer response.[11] Regulatory T cells have been shown to influence outcome to IL-2 and sunitinib therapy in metastatic RCC.[12,13]
To gain further insight into expression of markers potentially relevant to checkpoint inhibition in RCC, matched primary and metastatic RCC tumors were characterized. The availability of matched samples could provide insight into intrapatient heterogeneity regarding biomarker expression. Such heterogeneity may have several implications, including which tissue is characterized prior to treatment selection and organ-specific clinical responses.
RCC  immunotherapy  nivolumab 
11 days ago
How Tariffs Stained the Washing Machine Market - The New York Times
Tariffs of two varieties have pushed prices up

The washer-specific tariffs raised costs for importers like LG and Samsung. But another tariff issued by Mr. Trump, on imported steel, raised costs for some domestic manufacturers like Whirlpool, which took those companies by surprise.

Many manufacturers passed those higher costs on to consumers. Once stores worked their way through models that had been imported before tariffs hit, deflation gave way to sharp price increases.

After years of steady growth, sales reversed in 2018

A basic rule of economics is that when the price of something goes up, people buy less of it. That’s just what happened to washing machines.
Economics 
12 days ago
Opinion | The Fleecing of Millennials - The New York Times
Why is this happening? The main reason is a lack of economic dynamism. Not as many new companies have been forming since 2000 — for reasons that experts don’t totally understand — and existing companies have been expanding at a slower rate. (The pace of job cuts has also fallen, which is why the unemployment rate has stayed low.) Rather than starting new projects, companies are sitting on big piles of cash or distributing it to their shareholders.

This loss of dynamism hurts millennials and the younger Generation Z, even as baby boomers are often doing O.K. Because the layoff rate has declined since 2000, most older workers have been able to hold on to their jobs. For those who are retired, their income — through a combination of Social Security and 401(k)’s — still outpaces inflation on average.

But many younger workers are struggling to launch themselves into good-paying careers. They then lack the money to buy a first home or begin investing in the stock market. Yes, older workers face their own challenges, like age discrimination. Over all, though, the generational gap in both income and wealth is growing.
Economics  inequality 
12 days ago
How I switched from Ruby to Python - Sqreen Blog | Modern Application Security
Good article on moving from Ruby to Python

Company does security agents for web sites.
Ruby  Python  Security 
12 days ago
1 Woman, 12 Months, 52 Places - The New York Times
I was going on 40, feeling sad about being single, and contemplating a sabbatical from New York Magazine, where I’d worked for 17 years, when I clicked on The New York Times home page and saw something curious: A job listing in the most-read articles list. Did I want to travel around the world and document it? it asked. Sure I did! So did pretty much everyone. By the time I saw the listing, 3,500 people had already applied. The final number, they tell me, was 13,000.

The odds were so impossible and the selection process so mysterious that I couldn’t allow myself to get too excited. And then I got the incredible phone call telling me I had three weeks to pack up my apartment, say goodbye to everyone I knew, quit a workplace that felt like family and set out for a year on the road.
Travel  Jobs  psychology 
12 days ago
Countries With Zero Rating Have More Expensive Wireless Broadband Than Countries Without It | Electronic Frontier Foundation
When an ISP decides to exempt certain applications or services from cutting into a user's data cap, that's zero rating. And the evidence is in that it conclusively makes broadband more expensive.

A comprehensive multi-year study by the non-profit Epicenter.works, comparing the 30 member countries of the European Union (EU) on net neutrality enforcement, has found that zero rating business practices by wireless carriers have increased the cost of wireless data compared to countries without zero rating. This directly contradicts all of the assertions by major wireless carriers that their zero rating practices are “free data” for consumers.

Based on the evidence, zero rating not only serves as a means to enhance ISPs’ power over the Internet, but it’s also how they charge consumers more money for wireless service. Zero rating was originally going to be banned by the FCC under the General Conduct Rule, but when the FCC changed leadership the agency promptly green lighted and encouraged the industry to engage in zero rating practices before it began its repeal of net neutrality.

Zero Rating Is Anti-Competitive, Not “Free Data”
EU countries that do not have zero rating practices enjoyed a double digit drop in the price of wireless data after a year. In comparison, the countries with prevalent zero rating practices from their wireless carriers consistently saw data prices increase. This makes sense; carriers have an incentive to raise the costs of exploring alternatives in order to make their preferred, zero-rated choice of content more attractive. However, once that incentive is removed, the wireless carrier no longer has a reason to raise the cost of alternatives because nothing is given special treatment. In short, zero rating practices cost you more money.
Economics  network  Privacy 
13 days ago
Crownpoint Rug Auction
Second Friday of every month
Travel 
14 days ago
Nivolumab/Ipilimumab Improves HRQoL in Intermediate- and Poor-Risk RCC | PracticeUpdate
In early 2018, investigators of CheckMate 214 reported efficacy results of the randomized phase III trial comparing nivolumab plus ipilimumab with sunitinib in previously untreated patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC). Improved progression-free survival, overall survival, and objective response rate with the immunotherapy combination led to FDA approval of nivolumab plus ipilimumab as first-line therapy, establishing a new standard of care for intermediate- or poor-risk advanced RCC; however, a higher proportion of patients discontinued treatment in the nivolumab plus ipilimumab group than in the sunitinib group, leading to questions concerning health-related quality of life (HRQoL) with the combination.

Cella and colleagues further assess patient-reported outcomes (PROs) of the CheckMate 214 trial in a recent issue of The Lancet Oncology in order to characterize the benefit–risk profile of the nivolumab plus ipilimumab versus sunitinib. While on treatment, patients were asked to complete the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), Functional Assessment of Cancer Therapy-General (FACT-G), and EuroQol five-dimensional three-level (EQ-5D-3L) questionnaires. Investigators found that, over the first 103 weeks on study treatment, patients experienced improved HRQoL with nivolumab plus ipilimumab compared with sunitinib, with total scores from FKSI-19 and FACT-G instruments reaching statistical significance at times. Additionally, those with high baseline HRQol as well as improved HRQol from baseline were seen to have the longest overall survival in both treatment groups, suggesting that these points may be prognostic of survival. The data presented show that the combination of nivolumab plus ipilimumab has a superior benefit–risk profile as compared with sunitinib and support the combination as the new standard of care.

BACKGROUND

In the ongoing phase 3, CheckMate 214 trial, nivolumab plus ipilimumab improved overall survival compared with sunitinib in patients with intermediate or poor risk, previously untreated, advanced renal cell carcinoma. We aimed to assess whether health-related quality of life (HRQoL) could be used to further describe the benefit-risk profile of nivolumab plus ipilimumab versus sunitinib.

METHODS

In the phase 3, randomised, controlled, CheckMate 214 trial, patients aged 18 years and older with previously untreated, advanced or metastatic renal cell carcinoma with a clear-cell component were recruited from 175 hospitals and cancer centres in 28 countries. Patients were categorised by risk status into favourable, intermediate, and poor risk subgroups and randomly assigned (1:1) to open-label nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab 3 mg/kg every 2 weeks, or sunitinib 50 mg/day for 4 weeks of each 6-week cycle. Randomisation was done with a block size of four and stratified by risk status and geographical region. Patient-reported outcomes (PROs) were assessed using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), Functional Assessment of Cancer Therapy-General (FACT-G), and EuroQol five dimensional three level (EQ-5D-3L) instruments. The coprimary endpoints of the trial, reported previously, were overall survival, progression-free survival, and the proportion of patients who had an objective response in those categorised as at intermediate or poor risk. PROs in all randomised participants were assessed as an exploratory endpoint; here we report this exploratory endpoint. This study is registered with ClinicalTrials.gov, number NCT02231749, and is ongoing but is now closed to recruitment.

FINDINGS

Between Oct 16, 2014, and Feb 23, 2016, of 1390 patients screened, 1096 (79%) were randomly assigned to treatment, of whom 847 (77%) were at intermediate or poor risk and randomly assigned to nivolumab plus ipilimumab (n=425) or sunitinib (n=422). Median follow-up was 25·2 months (IQR 23·0-27·4). PROs were more favourable with nivolumab plus ipilimumab than sunitinib throughout the first 103 weeks after baseline, with mean change from baseline at week 103 for FKSI-19 total score being 4·00 (95% CI 1·91 to 6·09) for nivolumab plus ipilimumab versus -3·14 (-6·03 to -0·25) for sunitinib (p<0·0001), and for FACT-G total score being 4·77 (1·73 to 7·82) for nivolumab plus ipilimumab versus -4·32 (-8·54 to -0·11) for sunitinib (p=0·0005). Significant differences were also seen for four of five FKSI-19 domains (disease-related symptoms, physical disease-related symptoms, treatment side-effects, and functional wellbeing) and FACT-G physical and functional wellbeing domains. However, there was no significant difference between the treatment groups at week 103 in EQ-5D-3L visual analogue rating scale (VAS) scores, with mean change from baseline to week 103 of 10·07 (95% CI 4·35 to 15·80) for nivolumab plus ipilimumab and 6·40 (-1·36 to 14·16) for sunitinib (p=0·45). Compared with sunitinib, nivolumab plus ipilimumab reduced risk of deterioration in FKSI-19 total score (hazard ratio [HR] 0·54; 95% CI 0·46-0·63), FACT-G total score (0·63, 0·52-0·75), and EQ-5D-3L VAS score (HR 0·75, 95% CI 0·63-0·89) and UK utility scores (0·67, 0·57-0·80).

INTERPRETATION

Nivolumab plus ipilimumab leads to fewer symptoms and better HRQoL than sunitinib in patients at intermediate or poor risk with advanced renal cell carcinoma. These results suggest that the superior efficacy of nivolumab plus ipilimumab over sunitinib comes with the additional benefit of improved HRQoL.
RCC  nivolumab  immunotherapy  sunitinib 
14 days ago
GitHub - ankane/blazer: Business intelligence made simple
Explore your data with SQL. Easily create charts and dashboards, and share them with your team.
RubyOnRails  DataMining  datavisualization  gems 
15 days ago
Management of Brain Metastases in the Era of Checkpoint Inhibitors | PracticeUpdate
That’s why in the past, traditionally, brain metastases were handled by neurosurgeons or radiation oncologists. So, we used to take the brain mets out and then we used to give some focused forms of radiation. Either whole brain radiation or a focused form of radiation called stereotactic radiosurgery. However, this paradigm has changed significantly and there are two approaches to go on. One is a targeted therapy approach where you actually have drugs that will target particular molecule pathways that are actually driving the cancer cell. So, you typically target those mutations using targeted drugs and we use these tyrosine kinase inhibitors, which tend to be small drugs that easily traverse across the blood-brain barrier. The other approach is an immunotherapy-based approach where you actually boost someone’s immune system to go and kill the cancer cell. In the past, a brain was felt to be an immunoprivileged site. What that means is people thought that the immunotherapies would not work in the brain.

Now, we have several nature papers showing that’s not true. There is a trafficking of T cells going into the brain, there’s constant interaction with the cervical lymph nodes, so there is this crosstalk going on. And then there have been a number of clinical trials actually, which have clearly demonstrated that the immunotherapy works in the brain. And there are several trials that I would like to talk about today, which have shown the importance of immunotherapy in brain metastases. The first trial was a trial led by Kim Margolin, which was 72 patients. They gave the patients ipilimumab, which is a drug that targets the anti-CTLA-4, which is basically a negative immune checkpoint. This drug targets this checkpoint and activates the immune system. There were two cohorts. Cohort A was those patients who were not on steroids. Cohort B was 21 patients who were on steroids.

We’ve had three teaching points that we learned from that trial. The first one was that the drugs worked equally well in the brain as well as extracranially. The second was that the patients who were on steroids had less robust responses as compared to someone who was not on steroids. So, that means steroids impact response rate. You’ll have a higher response rate if you’re not on steroids. You’ll have a low response rate if you're on steroids. Albeit, we know generally large lesions tend to grow more rapidly and those are the patients, which need to be on steroids. The third teaching point from that trial that we learned was that the responses with immune checkpoint were durable. Most of the targeted therapies, when they work in brain metastases, typically have a response rate that lasts from 6 months to even 15 months with some of the new inhibitors, which are very exciting. But if you get a response rate with immune checkpoint, at least from the ipilimumab trial led by Kim Margolin, we have seen some of those patients to have responses 2, 3, even 5 years out, which is very exciting. Now, we have had several new immune checkpoint inhibitors that have come on since the ipilimumab.

Dr. Shah: Yes. So, I was going to ask you about that. So, if you do a dual checkpoint blockade would that help or is there one checkpoint blockade that seems to be better than the other?

Dr. Ahluwalia: So, great question. So, what we found with ipilimumab was the clinical benefit as they define in that trial was around 20 to 25%, at least in patients who are not on steroids. Patients who are on steroids, that benefit rate was around 10%. Then the new drugs came, which was the immune checkpoint blockade, which is the anti-PD-1 effort. There, we found single agent anti-PD-1 blockade produce response rates in the ballpark of 20 to 30% response rates with less toxicity than a drug like ipilimumab. Then the group of us got together and redesigned the next cadre of trials, which was one of the examples of checkpoint 204, in which we participated. Here, we combined both ipilimumab with nivolumab.

So, we’re now combining an anti-CTLA-4-based effort with an anti-PD-1 effort. And what we found was when we combine them in melanoma, our response rates were now 55%. So, we got 20 to 30% with one, got 20% or 25% clinical benefit rate over the one, and when we combined them we had much higher response rates. Albeit, there is slightly higher toxicity also, which is observed with the combination, because the ipilimumab or anti-CTLA-4 drugs tend to be more toxic than the anti-PD-1 drugs like pembrolizumab or nivolumab.

Dr. Shah: Now, would you expect there to be a difference in this therapy for, say, melanoma versus an NSCLC metastases or is there data showing a differential response?

Dr. Ahluwalia: So, great question. So, we do actually. There was a trial, which looked at pembrolizumab, which is one of the anti-PD-1 inhibitors, and they had two cohorts of it. This was a study led by Yale; Harriet Kluger and Sarah Goldberg led the effort. In melanoma, what the initial results that were published in The Lancet Oncology showed that 4 out of 18 melanoma patients had a response with single agent pembrolizumab, that is 22% response rate. Non-small cell lung cancer, on the other hand, 6 out of 18 patients had response rates, which amounted to 33% responses. Now, in melanoma, we have data with dual checkpoint blockade, as we discussed, which is 55% with both. In lung cancer, we still don’t have that data and there are ongoing trials looking at what will be the outcomes of these patients with the combination approach, which I believe is going to be higher based on our experience with melanoma.

Dr. Shah: And do you see any further combinations as being effective? So, that is, you take the single or dual checkpoint blockade inhibition and you combine that with, say, stereotactic radiation or some other existing therapy for brain mets. Do we have data on this and where do you see that field going?

Dr. Ahluwalia: So, great question. I think the field is going to go into combinatorial approaches now because traditionally, as we discussed, radiosurgery has been an important part of management of patients with brain metastases. Now, some of these immune checkpoint inhibitor studies that we discussed actually, typically, in well patients who are asymptomatic or who are low doses of steroids. Because immunotherapy doesn’t work very well if patients are on steroids. So, although there is no perspective data so far in combination, we have retrospective data.

In fact, we ourselves presented this data at ASTRO and several others have done it. And what we have found in at least retrospective experiences when we are combining stereotactic radiosurgery with immunotherapy, we are getting response rates, which are higher than at least with stereotactic radiosurgery alone in such patients. So, I think in the future trials will test this combination-based approach. One of the other challenges that we will want to address is what’s the right sequencing? Do you give the anti-PD-1 before you do radiosurgery or do you do radiosurgery first where the radiation can act as a new antigen expression-based approach and then you mount an anti-PD-1 approach on that? So, we and several others are working on this effort where we’re looking at scheduling and sequencing as well.
cancer  brainmets  immunotherapy  nivolumab  TKInhibitors 
16 days ago
Opinion | The Real Legacy of the 1970s - The New York Times
So that was the first change flowing from the Great Inflation: Americans became a more acquisitive — bluntly, a more selfish — people. The second change was far more profound.

For decades after World War II, the economic assumptions that undergirded policymaking were basically those of John Maynard Keynes. His “demand side” theories — increase demand via public investment, even if it meant running a short-term deficit — guided the New Deal, the financing of the war and pretty much all policy thinking thereafter. And not just among Democrats: Dwight Eisenhower and Richard Nixon were Keynesians.

There had been a group of economists, mostly at the University of Chicago and led by Milton Friedman, who dissented from Keynes. They argued against government intervention and for lower taxes and less regulation. As Keynesian principles promoted demand side, their theories promoted the opposite: supply side.

They’d never won much of an audience, as long as things were working. But now things weren’t, in a big way. Inflation was Keynesianism’s Achilles’ heel, and the supply-siders aimed their arrow right at it. Reagan cut taxes significantly. Inflation ended (which was really the work of Paul Volcker, the chairman of the Federal Reserve). The economy boomed. Economic debate changed; even the way economics was taught changed.

And this, more or less, is where we’ve been ever since. Yes, we’ve had two Democratic presidents in that time, both of whom defied supply-side principles at key junctures. But walk down a street and ask 20 people a few questions about economic policy — I bet most will say that taxes must be kept low, even on rich people, and that we should let the market, not the government, decide on investments. Point to the hospital up the street and tell them that it wouldn’t even be there without the millions in federal dollars of various kinds it takes in every year, and they’ll mumble and shrug.

There are signs this mind-set is changing. The Trump tax cut of 2017 is consistently unpopular. Representative Alexandria Ocasio-Cortez, Democrat of New York, speaks of a top marginal tax rate of 70 percent on income over $10 million, and instead of getting laughed out of town, she prompts a serious public debate.
Economics  History  Politics 
17 days ago
Teenagers who copy each other’s risk-taking have more friends | New Scientist
When the volunteers played the game alone, the boys were less likely than the men to take the risky gamble of trying for a larger payout. “There is this stereotype, but teens were not more risk-seeking when tested alone,” says Reiter.

However, this changed when the participants no longer thought they were alone. In a second run of the experiment, the volunteers met a “partner” face-to-face before playing the game, and were told they could see each other’s actions on a computer. In reality, the researchers were in control of all the “partner’s” decisions.

Read more: Revealed: the teenage brain upgrades that occur before adulthood
If the fake partner took the risky gamble more often, the boys’ own play became riskier – but only if their partner was another teen, not an adult. The boys’ behaviour changed more than twice as much as that of the adults.

A questionnaire revealed that the boys who changed their behaviour the most also reported having more friends and a higher social confidence.

These findings don’t prove that taking more risks is a direct cause of popularity, but they do hint at a link. “The idea of ‘risk contagion’ has this passive connotation, like these empty-headed teenagers are being infected with something,” says Gabriele Chierchia of University College London. “But it may be an active effort. There’s probably something adaptive going on.”

Reiter suggests that teenage bloggers and YouTube stars should be more aware of their potential influence over their audience. “You might see YouTubers that are risk-taking and you might also see YouTubers that are suggesting nice things. [Copying behaviour] is not necessarily something bad, it’s just a natural thing in adolescence.”

In a previous study, smoking rates at a school were cut by identifying its most influential pupils and getting them to discourage others from starting.
psychology 
18 days ago
People with depression are less likely to have certain gut bacteria | New Scientist
People who lack certain gut bacteria are more likely to experience depression, according to the largest study yet to find a link between our microbiota and mental health.

Jeroen Raes of KU Leuven University in Belgium and colleagues examined over 1000 volunteers in Belgium who’d had the bacteria living in their gut genetically sequenced as part of a larger study.

The team found that two kinds of bacteria, Dialister and Coprococcus, were less common in people who reported that they were depressed. The same result was seen in a second group of over 1000 volunteers from the Netherlands.


Read more: An inflamed brain may be a hidden cause of depression
This doesn’t necessarily mean that lacking these bacteria causes depression. It could be that people who have depression eat differently, for instance, and that this changes their gut flora. “To determine causality, we would need to procure these bugs and give them to mice with a version of depression,” says Raes.

But if the bacteria do play a role in preventing depression, it could be because both these microbes make an anti-inflammatory compound called butyrate, says Raes. A growing body of research has suggested the mood disorder could be caused, at least in some people, by ongoing systemic inflammation.

Journal reference: Nature Microbiology, DOI: 10.1038/s41564-018-0337-x
depression  psychology  microbiome 
18 days ago
[1901.05350] TensorFlow.js: Machine Learning for the Web and Beyond
TensorFlow.js: Machine Learning for the Web and Beyond
Daniel Smilkov, Nikhil Thorat, Yannick Assogba, Ann Yuan, Nick Kreeger, Ping Yu, Kangyi Zhang, Shanqing Cai, Eric Nielsen, David Soergel, Stan Bileschi, Michael Terry, Charles Nicholson, Sandeep N. Gupta, Sarah Sirajuddin, D. Sculley, Rajat Monga, Greg Corrado, Fernanda B. Viegas, Martin Wattenberg
(Submitted on 16 Jan 2019)
TensorFlow.js is a library for building and executing machine learning algorithms in JavaScript. TensorFlow.js models run in a web browser and in the Node.js environment. The library is part of the TensorFlow ecosystem, providing a set of APIs that are compatible with those in Python, allowing models to be ported between the Python and JavaScript ecosystems. TensorFlow.js has empowered a new set of developers from the extensive JavaScript community to build and deploy machine learning models and enabled new classes of on-device computation. This paper describes the design, API, and implementation of TensorFlow.js, and highlights some of the impactful use cases.
machinelearning  ai  JavaScript 
18 days ago
America colonisation ‘cooled Earth's climate’ - BBC News
Where's the support for the connection?
The drop in CO₂ at the time of the Great Dying is evident in the ice core records from Antarctica.
Air bubbles trapped in these frozen samples show a fall in their concentration of carbon dioxide.
The atomic composition of the gas also suggests strongly that the decline is being driven by land processes somewhere on Earth.
In addition, the UCL team says the story fits with the records of charcoal and pollen deposits in the Americas.
These show the sort of perturbation expected from a decline in the use of fire to manage land, and a big grow-back of natural vegetation.
Ed Hawkins, professor of climate science at Reading University, was not involved in the study. He commented: "Scientists understand that the so-called Little Ice Age was caused by several factors - a drop in atmospheric carbon dioxide levels, a series of large volcanic eruptions, changes in land use and a temporary decline in solar activity.
"This new study demonstrates that the drop in CO₂ is itself partly due the settlement of the Americas and resulting collapse of the indigenous population, allowing regrowth of natural vegetation. It demonstrates that human activities affected the climate well before the industrial revolution began."
Are there lessons for modern climate policy?
Co-author Dr Chris Brierley believes there is. He said the fall-out from the terrible population crash and re-wilding of the Americas illustrated the challenge faced by some global warming solutions.
"There is a lot of talk around 'negative emissions' approaches and using tree-planting to take CO₂ out of the atmosphere to mitigate climate change," he told BBC News.
"And what we see from this study is the scale of what's required, because the Great Dying resulted in an area the size of France being reforested and that gave us only a few ppm. This is useful; it shows us what reforestation can do. But at the same, that kind of reduction is worth perhaps just two years of fossil fuel emissions at the present rate."
Science  History  climate 
18 days ago
We may finally know what causes Alzheimer’s – and how to stop it | New Scientist
The speed at which damage accumulates is a key factor in the disease. Although many people harbour P. gingivalis in their mouths, only some develop Alzheimer’s. Because it can be decades before Alzheimer’s symptoms appear, whether a person develops the condition could come down to how much damage occurs before they die of other causes.

“Alzheimer’s strikes people who accumulate gingipains and damage in the brain fast enough to develop symptoms during their lifetimes,” says Lynch. She says her team’s findings are a “universal hypothesis of pathogenesis”, fully explaining the causes of Alzheimer’s disease.

But Vissel warns that Alzheimer’s is a complex disease. “The answer is unlikely to be one-cause-fits-all. We need to keep open eyes.”

However, the new study is “very exciting”, he says. “Alzheimer’s is so common in people at advanced age that I think it can only be either some intrinsic property of the brain, or an infection.”

If this new hypothesis of Alzheimer’s is borne out, the good news is that it could lead to effective treatments for the condition. Although there is plenty you can do to reduce your risk of gum disease, Cortexyme is hoping it can stop or even reverse Alzheimer’s using molecules it has developed that block gingipains. The firm found that giving some of these to mice with P. gingivalis infections reduced brain infection, halted amyloid production, lowered brain inflammation and even rescued damaged neurons. “This provides hope of treating or preventing Alzheimer’s disease one day,” says Singhrao.

Cortexyme reported last year that the best of its gingipain blockers had passed initial safety tests in people, and entered the brain. It also seemed to improve symptoms in participants with Alzheimer’s. The firm will launch a larger trial later this year.

The company also plans to test the drug against gum disease itself. Efforts to fight that have led a team in Melbourne to develop a vaccine for P. gingivalis that started tests in 2018. A vaccine for gum disease would be welcome – and if it also stops Alzheimer’s the impact could be enormous.

It is early days for this new hypothesis, and if the pursuit of amyloid-busting drugs over the past few decades has taught us anything, says Vissel, it is that a complex disease may not have a simple mechanism. Even if P. gingivalis is confirmed as a cause of Alzheimer’s, we don’t know yet whether it will turn out to be the only cause or one of several factors contributing to the disease.

“This paper is very important,” says George Perry at the University of Texas at San Antonio. “The view that pathogens might be one of several paths leading to Alzheimer’s disease fits my current thoughts of amyloid and tau being critical brain responses to injury, instead of the initiators.”

That, he says, is why years of efforts to treat Alzheimer’s by removing those proteins have seen few results: they are symptoms of the disease, not its cause. “This is a further turning point in the understanding that infections and inflammation can be at the heart of Alzheimer’s disease.”
Science  health  dementia 
18 days ago
Now for the Hard Part: Getting Californians to Buy Legal Weed - The New York Times
SAN FRANCISCO — A billion dollars of tax revenue, the taming of the black market, the convenience of retail cannabis stores throughout the state — these were some of the promises made by proponents of marijuana legalization in California.

One year after the start of recreational sales, they are still just promises.

California’s experiment in legalization is mired by debates over regulation and hamstrung by cities and towns that do not want cannabis businesses on their streets.

California was the sixth state to introduce the sale of recreational marijuana — Alaska, Colorado, Nevada, Oregon and Washington paved the way — but the enormous size of the market led to predictions of soaring legal cannabis sales.

Instead, sales fell. Around $2.5 billion of legal cannabis was sold in California in 2018, half a billion dollars less than in 2017 when only medical marijuana was legal, according to GreenEdge, a sales tracking company.
weed  Economics  SoCal 
20 days ago
The hoarding gene: Using the behavior of Doberman pinschers to understand the compulsion to collect
In one revealing study, we focused on a bizarre behavior called flank sucking. An affected Doberman will put its open mouth on its flank, clamp down softly and, adopting a dreamy look, begin sucking. After questioning almost a hundred owners of flank-sucking Dobermans and an equal number of Doberman owners whose dogs do not engage in the behavior, we found that flank suckers also have a strong penchant for gathering, mouthing and ingesting non-food substances.

Granted, many dogs do such things, but these Dobermans do them persistently and compulsively, in much the way that humans suffering from obsessive-compulsive disorder might repeatedly wash their hands.

They fetishize a wide variety of materials, including fabrics (blankets, socks, toy stuffing, sneakers and crate pads), organic matter (dirt, leaves, branches and twigs), paper products (sheets of paper, paper towels, cardboard, dryer sheets, cotton-tipped swabs and cigarette butts), plastic and vinyl (toys, jump drives, cell phones, pagers, pens, electric toothbrushes, shavers, eyeglasses and remote controls) and metal (nuts, bolts and keys). Some dogs simply lick the objects or carry them around, often bringing them to a particular location. Doberman owners call this behavior "shopping."

One video that went viral shows a Doberman that appears to have developed an interesting version of this shopping habit. The dog would arrange three Beanie Babies of the same type, face up, in a triangular pattern. Then it would arrange other toys—always the same type—in a straight line. One day this dog, an aloof rescue animal, finally allowed its owner to give it a big hug.
dogs  psychology 
20 days ago
Sapwood
Sapwood doesn't judge. It's not that it's aloof. It cares about you very much. It wants to be the content mechanism behind your next great idea. But it lets you design your own content structure, and it wants you to use the tools you already love to surface your content in any way you can dream it.
CMS  RubyOnRails 
20 days ago
Dramatiq: simple task processing — Dramatiq 1.4.3 documentation
Dramatiq is a distributed task processing library for Python with a focus on simplicity, reliability and performance.


Here’s what it looks like:

import dramatiq
import requests

@dramatiq.actor
def count_words(url):
response = requests.get(url)
count = len(response.text.split(" "))
print(f"There are {count} words at {url!r}.")

# Synchronously count the words on example.com in the current process
count_words("http://example.com")

# or send the actor a message so that it may perform the count
# later, in a separate process.
count_words.send("http://example.com")
Dramatiq is licensed under the LGPL and it officially supports Python 3.5 and later.
Python  celery  Redis 
22 days ago
The Real Reason the U.S. Has Employer-Sponsored Health Insurance - The New York Times
The basic structure of the American health care system, in which most people have private insurance through their jobs, might seem historically inevitable, consistent with the capitalistic, individualist ethos of the nation.

In truth, it was hardly preordained. In fact, the system is largely a result of one event, World War II, and the wage freezes and tax policy that emerged because of it. Unfortunately, what made sense then may not make as much right now.

Well into the 20th century, there just wasn’t much need for health insurance. There wasn’t much health care to buy. But as doctors and hospitals learned how to do more, there was real money to be made. In 1929, a bunch of hospitals in Texas joined up and formed an insurance plan called Blue Cross to help people buy their services. Doctors didn’t like the idea of hospitals being in charge, so some in California created their own plan in 1939, which they called Blue Shield. As the plans spread, many would purchase Blue Cross for hospital services, and Blue Shield for physician services, until they merged to form Blue Cross and Blue Shield in 1982.

Most insurance in the first half of the 20th century was bought privately, but few people wanted it. Things changed during World War II.

---
This system is expensive. The single largest tax expenditure in the United States is for employer-based health insurance. It’s even more than the mortgage interest deduction. In 2017, this exclusion cost the federal government about $260 billion in lost income and payroll taxes. This is significantly more than the cost of the Affordable Care Act each year.

This system is regressive. The tax break for employer-sponsored health insurance is worth more to people making a lot of money than people making little. Let’s take a hypothetical married pediatrician with a couple of children living in Indiana who makes $125,000 (which is below average). Let’s also assume his family insurance plan costs $15,000 (which is below average as well).

The tax break the family would get for insurance is worth over $6,200. That’s far more than a similar-earning family would get in terms of a subsidy on the exchanges. The tax break alone could fund about two people on Medicaid. Moreover, the more one makes, the more one saves at the expense of more spending by the government. The less one makes, the less of a benefit one receives.

The system also induces people to spend more money on health insurance than other things, most likely increasing overall health care spending. This includes less employer spending on wages, and as health insurance premiums have increased sharply in the last 15 years or so, wages have been rather flat. Many economists believe that employer-sponsored health insurance is hurting Americans’ paychecks.
Economics  HealthCare  History 
22 days ago
American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. - PubMed - NCBI
The 2015 American Geriatrics Society (AGS) Beers Criteria are presented. Like the 2012 AGS Beers Criteria, they include lists of potentially inappropriate medications to be avoided in older adults. New to the criteria are lists of select drugs that should be avoided or have their dose adjusted based on the individual's kidney function and select drug-drug interactions documented to be associated with harms in older adults. The specific aim was to have a 13-member interdisciplinary panel of experts in geriatric care and pharmacotherapy update the 2012 AGS Beers Criteria using a modified Delphi method to systematically review and grade the evidence and reach a consensus on each existing and new criterion. The process followed an evidence-based approach using Institute of Medicine standards. The 2015 AGS Beers Criteria are applicable to all older adults with the exclusion of those in palliative and hospice care. Careful application of the criteria by health professionals, consumers, payors, and health systems should lead to closer monitoring of drug use in older adults.
pharmacology 
22 days ago
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